Neutron crystallography reveals mechanisms used by Pseudomonas aeruginosa for host-cell binding

• Published in: Nature communications Vol. 13; no. 1; p. 194
• Main Authors: Gajdos, Lukas, Blakeley, Matthew P., Haertlein, Michael, Forsyth, V. Trevor, Devos, Juliette M., Imberty, Anne
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11-01-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326/41/2536; 631/45/221; 631/45/72; 631/535/1266; 82/80; Affinity; Bacterial Adhesion - genetics; Bacterial diseases; Bacteriology; Basic Medicine; Binding Sites; Biochemistry and Molecular Biology; Biochemistry, Molecular Biology; Biofilms; Biokemi och molekylärbiologi; Biologi; Biological Sciences; Bronchopulmonary infection; Calcium; Calcium - metabolism; Calcium ions; Carbohydrates; Cloning, Molecular; Cross Infection - microbiology; Crystal structure; Crystallography; Crystallography, X-Ray; Deuteration; Deuterium - chemistry; Escherichia coli - genetics; Escherichia coli - metabolism; Fucose; Fucose - chemistry; Fucose - metabolism; Galactose; Gene Expression; Genetic Vectors - chemistry; Genetic Vectors - metabolism; Humanities and Social Sciences; Humans; Hydrogen; Hydrogen atoms; Hydrogen Bonding; Hydrogen bonds; Ions; Lectins; Lectins - chemistry; Lectins - genetics; Lectins - metabolism; Life Sciences; Ligands; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Microbiology and Parasitology; Microbiology in the medical area; Mikrobiologi inom det medicinska området; multidisciplinary; Natural Sciences; Naturvetenskap; Neutrons; Nosocomial infection; Nosocomial infections; Opportunist infection; Pathogenicity; Pathogens; Protein Binding; Proteins; Protonation; Pseudomonas aeruginosa; Pseudomonas aeruginosa - chemistry; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - metabolism; Pseudomonas Infections - microbiology; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Room temperature; Science; Science (multidisciplinary); Structural Biology; Water - metabolism; Water chemistry
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27871-8

The opportunistic pathogen
Pseudomonas aeruginosa
, a major cause of nosocomial infections, uses carbohydrate-binding proteins (lectins) as part of its binding to host cells. The fucose-binding lectin, LecB, displays a unique carbohydrate-binding site that incorporates two closely located calcium ions bridging between the ligand and protein, providing specificity and unusually high affinity. Here, we investigate the mechanisms involved in binding based on neutron crystallography studies of a fully deuterated LecB/fucose/calcium complex. The neutron structure, which includes the positions of all the hydrogen atoms, reveals that the high affinity of binding may be related to the occurrence of a low-barrier hydrogen bond induced by the proximity of the two calcium ions, the presence of coordination rings between the sugar, calcium and LecB, and the dynamic behaviour of bridging water molecules at room temperature. These key structural details may assist in the design of anti-adhesive compounds to combat multi-resistance bacterial infections.
Pseudomonas aeruginosa
employs lectins to bind to its host cells, and is known to be the major cause of lung infections. Lectin B (LecB) from
Pseudomonas aeruginosa
binds specifically to galactose and fucose and is important for pathogenicity, adhesion and biofilm formation. In this work, the neutron crystal structure (1.9 Å) of the deuterated LecB/Ca/fucose complex is reported. The structure, in combination with perdeuteration of the ligand and the receptor allowed the observation of hydrogen atoms, protonation states and hydrogen bonds involved in the interaction between pathogenic bacteria and host cells. Thus the study provides structural insights into the mechanism of high affinity binding of LecB to its targets.